Case Presentation22 yo U.S. Army Active Duty male deployed to

Afghanistan west of Kandahar presents with fever (102.5o F), headache, fatigue, chills, abdominal pain with non-bloody diarrhea (SEP 8)Symptoms progressing over the previous 4 days

Initially told he had a “gastroenteritis” at local clinicTreated with Cipro and immodium48 hour quarters

Returned the following day (SEP 9):Symptoms worsening, now with nausea/vomiting and

lethargyTold he may have a “viral syndrome”Referred to Kandahar for observation

Case PresentationProgressively worsened over the next several

hoursLethargy lead to somnolence Bloody diarrhea and bleeding gumsShortness of breath intubatedAnemic, low platelets, developing organ failure

Evacuated to LRMC with presumed diagnosis of pneumonia with septic shock (antibiotics started)

Case PresentationUpon arrival at the Landstuhl Regional Medical

Center, he is found to be bleeding EVERYWHEREPetechiae everywhereLarge ecchymotic lesions at IV sitesExtremely sick

He requires emergent bronchoscopy for bleeding

The ICU staff raises the concern for viral hemorrhagic fever

Case PresentationCo-located with Afghan army

Potential exposuresNumerous outdoor activities to include sleeping

outsideRecent tick exposures

Patient and battle buddy both with recent bites within a week of illness onset

This was a common occurrence (bragging rights)

Exposure to goat blood and undercooked goat meat

Blood sent to the Bernard Nocht Institute (BNI) in Hamburg within hours of admission

Blood run overnightSEP 10: PCR and IGM POSITIVE for CCHFInfectious diseases consulted just prior to test results

Within ~12 hours of diagnosis, treatment with oral ribavirin thru feeding tubeDose given to match the standard IV dose

Emergency IND approval for IV ribavirin from the FDA

IV ribavirin started 12 hours after oral treatment (48 hours of hospitalization)

Case Presentation

Renal and hepatic dialysis startedPatient appeared to be improving

However:SEP 14

Patient had a asystolic/PVA arrestsDeclared brain dead

At time of death, viral load had declined and antibodies present

Case Presentation

Viral Hemorrhagic Fevers

Kris Paolino, MD, MTM&HInfectious Disease Staff

Chief, Clinical Trials CenterTranslational Medicine Branch

Walter Reed Army Institute of Research

Will Cover Some Steps to Avoid….

The “Slammer”

1995 Kikwit Zaire ZEBOV OutbreakCourtesy of Don Noah

OutlineVHFs in generalEpidemiologyClinical aspectsDiagnosisPreventive measuresTreatment

United State Army Medical Research Institute of Infectious Diseases (USAMRIID):

Potential of VHF’s for WeaponizationPRO

Many demonstrated as infectious by aerosol transmission Exception is Dengue

Potentially high morbidity and mortalityReplicate well in cell culture

Exception are viruses in Bunyaviridae (e.g. CCHF)

Capability to overwhelm medical resourcesFrightening effects of illness / terror value

CONLack of treatment or vaccine to protect user’s own “troops”

May not be deterrent for some countries / non-state actors

Possible entry into local vector / reservoir populationStabilizers must be used to enhance viability

Other Military Relevance: History of Weaponization

Yellow fever and RVF were weaponized by the U.S. during their offensive program

Former Soviet Union produced large quantities of Ebola, Marburg, Lassa, Junin, and Machupo

Yellow fever may have been weaponized by North Koreans

The Aum Shinrikyo cult unsuccessfully tried to obtain Ebola virus to create biological weapons

Several studies have demonstrated ability to aerosolize Ebola, Marburg, Lassa, and some of the New World arenaviruses

Definition• Viral hemorrhagic fever (VHF):• Fever • Malaise• Myalgia prostration• Bleeding diathesis• Enveloped, single-stranded, RNA viruses

• Hemorrhagic fever virus (HFV) is a term used to generically identify those agents that cause VHF.

Know What’s There and How You Can Get It

Courtesy of Mike Bray, NIAID

Alkhurma

Lujo

CCHF

CCHF

Overview of Etiologic Agents of VHFs

Family Genus Species

Filoviridae Ebolavirus Zaire, Sudan, Ivory Coast, Reston,

BundibugyoMarburgvirus Lake Victoria marburgvirus

Arenaviridae Arenavirus Lassa, Lujo (“Old World”)Junin, Machupo, Guanarito, Sabia, (“New World”)

Bunyaviridae Nairovirus Crimean-Congo hemorrhagic fever Phlebovirus Rift Valley fever

Hantavirus Hantaan, Seoul, Puumala, Dobrava, Sin Nombre

Flaviviridae Flavivirus Omsk HFKyasanur forest disease (including Alkhurma)DengueYellow fever

Overview of Epidemiology of HFVsNatural Other Incubation

Disease (virus) Distribution Host/ Sources (days)

Vector

Filoviruses

Ebola HF Africa, Philippines (ER) Bats? Nosocomial 2-21Marburg HF Africa Bats? Nosocomial 5-10

ArenavirusesLassa fever and Lujo virus Africa Rodent Nosocomial 5-16Argentine HF (Junin) South America Rodent Nosocomial 7-14Bolivian HF (Machupo)South America Rodent Nosocomial 9-15Venezuelan HF (Guanarito) South America Rodent Nosocomial 7-14Brazilian HF (Sabia) South America Rodent Nosocomial 7-14

BunyavirusesCCHF Europe, Asia, Africa Tick Animal slaughter, Nos. 3-12Rift Valley fever Africa Mosquito Animal slaughter 2-6HFRS/HPS (Bunyaviridae) World-wide Rodent 9-35

FlavivirusesOmsk HF Soviet Union Tick 2-9Kyasanur forest disease India Tick 2-9Dengue HF Asia, Americas, Africa Mosquito 3-15Yellow fever Africa, tropical America Mosquito 3-6Alkhumra HF Saudi Arabia, EgyptTick 2-9

How are VHFs Spread?1 – Inhaling or ingesting excretions/secretions

from rodent hosts (urine, feces)

2 - Bite of an infected arthropod (tick, mosquito)

3 – Nosocomial/lab transmission – contact with human or animal blood/body fluids/tissue

4 - Artificially generated aerosols (biowarfare)

Crimean Congo Hemorrhagic Fever

How are VHFs spread?In NHPs – possible airborne transmission

between cages 3 meters apartLung tissue with documented virus

In NHPs and GPs: infective via airborne, conjunctival, oral exposure

Viremia – 3-5 days1 day prior or simultaneous with clinical illness

(D4-5)Virus recovered from nares, pharynx, conjunctivae,

anus (days 7-10; limited numbers)

Lancet 1995;346:1669-71. Arch Virol 1996(suppl);11:115-134.

Arch Pathol Lab Med 1996;120: 140-5. Int J Exp Path 1995;76:227-36.

VHF Human-to-human transmissionOnly dengue and yellow fever virus have adapted

to efficient human-to-human transmission (via mosquitoes).For other HF viruses, humans are “dead-end” hosts.

Typical story for nosocomial transmission:Uncertain how first human/NHP is infectedPatient enters the health care facility

VHF is not recognized or infection control procedures are not followed

Unrecognized nosocomial spread from blood/body fluid contact

Health care personnel among the victims Victims carry infection to the community

Close family members and those doing burial rites facilitate further spread

No proven human to human respiratory transmission

How are VHFs Spread Person to Person?Usually spread during patient care without

appropriate barrier precautionsContact with blood/tissue/body fluids Includes re-use of syringes/needles

Epidemiologically, VHFs not readily transmitted person-to-person by airborne routeA possibility in only rare circumstances

Highest risk in later stages, when having vomiting, diarrhea, shock, hemorrhage

Not reported during incubation period (before fever)

MMWR 1995;44(25):475-79.

Know What They Can do

Model of Filoviral Pathogenesis in Primates

1

6

54 32

VHF: Spectrum of Clinical Presentations

Variety of presentationsProdrome

High fever, Headache, Malaise, Arthralgias, MyalgiasNausea, Abdominal pain, Non-bloody diarrhea

Early signsFever, Tachycardia, Tachypnea, Conjunctivitis,

PharyngitisFlushing, Skin Rash

Late↓ BP, Hemorrhagic diathesis, Petechiae, Mucous

membraneConj. hemorrhage, Hematuria, Hematemesis, Melena

Major ManifestationsDIC, Circulatory Shock, CNS dysfunction

Argentine Hemorrhagic Fever (Junin virus – New World Arenavirus )

Gingival hemorrhage

Ref: Current Science/Current Medicine (Peters CJ, Zaki SR, Rollin PE). Viral hemorrhagic fevers. In: Fekety R, vol ed. Atlas of Infectious Diseases, p10.1-10.26, Volume VIII, 1997.

Bolivian Hemorrhagic Fever(Machupo virus – New World Arenavirus)

Conjunctival injection & subconjunctival hemorrhage

Left arm. Ecchymosis, diffuse, severe. (1 week after clinical onset)

CCHF

Photo credit: Robert Swaneopoel, PhD, DTVM, MRCVS, National Institute of Virology, Sandringham, South Africa.

DENGUE

CCHF

KOREAN HEMORRHAGIC FEVER (HANTAAN)

DENGUE

BOLIVIAN HEMORRHAGIC FEVER (MACHUPO)

KOREAN HEMORRHAGIC FEVER (HANTAAN)

CCHF

CCHF

DENGUE

Photo credit: Martini GA, Knauff HG, Schmidt HA, et. al. Ger Med Mon. 1968:13:457-470.

Marburg Infection Human

Maculopapular rash

Clinical Features - VHF

Courtesy of Drs. Zaki & Peters

VHF: Spectrum of Laboratory AbnormalitiesLeukopenia

Lassa with leukocytosis (WBC inc.)

AnemiaHemoconcentrationThrombocytopeniaElevated liver enzymesMay have renal dysfunctionCoagulation abnormalities

VHF: Spectrum of Laboratory AbnormalitiesCoagulation

abnormalitiesProlonged bleeding

timeProthrombin timeActivated PTT↑ fibrin degradation↓ fibrinogen

UrinalysisProteinuri

aHematuriaOliguria Azotemia

VHFs With Known Nosocomial SpreadFiloviruses – Ebola and MarburgArenaviruses – Lassa, Junin/Machupo (rare)Bunyaviruses – CCHF, Andes virus (a cause

of hantavirus pulmonary syndrome)Flaviviruses – dengue (rare – from blood

splash)

Lassa – most common imported VHF (if dengue not included)

The “Deadly” VHFsVIRUS Mortality Rate

Ebola Zaire 75-90%

Marburg 25-90% Lassa 15-20% of hospitalized

CCHF 3-70% (typically 20-30%)

Rift Valley fever 50% of patients with hemorrhagic form

Potential distinguishing featuresJaundice/icterus

YF,RVF, CCHF, filoviruses (rare)

Renal failureHantaan/hantaviruses, YF

EncephalopathySouth American HFs, Filoviruses, YF, Omsk, Kyasanur

RashDengue, filoviruses, Lassa

How to Diagnose

Differential DiagnosisDistribution of CCHFDistribution of RVF

Distribution of Malaria

Distribution of CCHF

Distribution of RVF

Distribution of Junin

Antiviral Res 2008:132-39.

Differential Diagnosis of VHF

Clinical presentation: Fever, hemorrhage/purpura, thrombocytopenia, CNS signs, elevated LFTs, leukopenia, thrombocytopenia, DIC, multisystem / multi-organ failure

MalariaTyphoid fever Rocky Mountain Spotted Fever (Rickettsia rickettsii) & other rickettsiosesLeptospirosisMeningococci Q fever (Coxiella burnetti)Plague Influenza Viral meningitis / encephalitis (e.g. henipaviruses)HIV / co-infectionHemorrhagic smallpoxVasculitis (i.e. autoimmune diseases)Thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic

syndrome (HUS)

Diagnosis - Clinical Pathology

Thrombocytopenia or abnormal platelet functionLeukopenia (exception is Lassa, which has a

leukocytosis)Some patients have anemiaMost have elevated liver enzymes (ALT / AST)Bilirubin is elevated in RVF and YFProthrombin time, activated partial thromboplastin

time (APTT) and bleeding time are prolonged Some have disseminated intravascular coagulation

(DIC); those that have DIC have elevated d-dimers (FDP’s) and decreased fibrinogen

These are not hard and fast rules. There will be overlap with many of these infections.

Diagnosis - Laboratory Confirmation

Gold Standard - Virus isolation from blood, serum or tissue biopsyBSL-4 Lab

Electron microscopyReverse transcription - polymerase

chain reaction (RT-PCR)Increasingly important tool

Rapid ELISA techniques most easily employedAntigen capture detectionIgM (test of choice for Hantaviridae, yellow

fever, & Dengue) or IgG antibody capture

Serology on paired sera (acute and convalescent)

Immunohistochemistry (IHC) & in situ hybridization (ISH) of infected tissues Formalin-fixed tissue CDC has developed a skin biopsy procedure for

detection of EBOV using IHC

Diagnosis - Laboratory Confirmation

Know How to Protect Yourself and Others

Prevention / ControlYELLOW FEVER

Licensed 17D vaccine, highly efficaciousLive virus vaccineReports of vaccine associated deathsCannot be used in persons with egg allergy

Junin Candid 1 – ARGENTINE HFLive, attenuatedSafe and efficaciousProtects monkeys against Bolivian HFNOT AVAILABLE IN THE UNITED

STATES

Prevention / Control:None Licensed

Rift Valley Fever Formalin-inactivated

safe but requires 3 shots, intermittent booster limited supply

Live, attenuated MP-12 Phase II testing

EbolaAdenovirus vectored +/- DNA primeVEE repliconsVSV vectoredVirus-like particles (VLP)

MarburgRecent NHP study at USAMRIID: 100% survival following

challenge w/ lethal dose of MBGV and then post-exposure treatment w/ recombinant VSV-GP Marburg vaccine

VHF Spread Summary – lack of spread1967 – Marburg – no airborne transmission1975 – 2 pts, Marburg in S. Africa

1/35 HCWs infected when barrier precautions not used

1979 – 34 pts, Ebola in Southern Sudan29 cases – direct contact0 cases of 103 who had no direct contact

1994 – 1 pt, Ebola1/70 contacts infected (no airborne precautions)

1996 – 2 pts, Ebola0/300 contacts infected

VHF Spread Summary – evidence of spread1995 – 316 infected with Ebola in DRC

3 HCPs infected after “barrier precautions” 1 – non-adherent 1 – needlestick 1 – uncertain - ? Rubbed eyes with glove

No household non-physical contacts infected

2000 – 224 deaths, Ebola in Uganda14/22 (64%) infected after infx controlUncertain why this happenedCouldn’t rule out airborne transmission

Conclusion:Preponderance of evidence: Can’t r/o airborne

transmission, but appears to be a minor mode if it exists

Transmission rarely, if ever occurs prior to onset of signs/symptoms

Number of infected health care workers declined after barrier nursing practices were begun during the Ebola HF outbreak in Kikwit, DRC, 1995.

Critical Care Clinics (2005) 21:765-783.

Back to the initial case…18 healthcare providers identified as being

HIGH risk exposuresOffered oral ribavirin post-exposure

prophylaxis2 individuals had more significant symptoms to

medsBoth were found to have developed antibodies

to the CCHF virus

1995 Kikwit Zaire ZEBOV OutbreakCourtesy of Don Noah

Outbreak Management:IsolationBarrier precautions

CDC Recommendations - when to go “hot”Standard Precautions in initial assessmentsPrivate room upon initial hospitalization

Barrier precautions – including face shields, surgical masks, eye protection within 3 feet of patient

Negative pressure room not required initially, but should be considered early to prevent later need for transfer

Airborne precautions if prominent cough, vomiting, diarrhea, hemorrhageE.g. HEPA masks, negative pressure isolation

MMWR 1988;37(S-3):1-16. MMWR 1995;44(25):475-79.

•

www.cdc.gov/ncidod/dvrd/spb/mnpages/vhfmanual.htm

Standard Precautions for All PatientsIdentify a minimum level of Standard

Precautions Establish routine hand washingEstablish safe handling and disposal of used

needles and syringesBe prepared to intensify Standard Precautions

and include VHF isolation precautionsIdentify a VHF coordinator to oversee and

coordinate activities associated with VHF isolation precautions

WHO VHF Africa Manual

Use VHF Isolation PrecautionsIsolate the patientWear protective clothing:

Scrub suit, gown, apron, two pairs of gloves, mask, headcover, eyewear, rubber boots

Clean/disinfect spills, waste, and reusable safety equipment, soiled linens, and laundry safely

Use safe disposal methods for non-reusable supplies and infectious waste

Counsel staff about the risk of VHF transmissionProvide information to families and the

community about VHF prevention and care of patients

WHO VHF Africa Manual

Selection Site for Isolation Area (if isolation area not available)

Single room with adjoining toilet or latrineSeparate building or ward for VHF

patients onlyAn area in a larger ward that is separate

and far away from other patientsAn uncrowded corner of a large room or

hallAny area that can be separated from the

rest of the health facility

WHO VHF Africa Manual

Infection ControlSingle room with adjoining anteroom

as only entranceChanging area/protective equipmentDisinfection solutions

0.5% sodium hypochlorite, 2% glutaraldehyde, phenolic disinfectants (0.5%-3.0%), soaps and detergents

Hand washing stationsChemical toilets

WHO VHF Africa Manual

Other Isolation PrecautionsLimit health facility staff and visitors in the

patient’s roomDevelop and post an “authorized” list for entryProvide a guard with the list

Limit use of invasive procedures and reduce injectable medicines

WHO VHF Africa Manual

Medical ManagementFirst Aid for Exposures

Anticipate in advance – be preparedWash / irrigate wound or site immediately

within 5 minutes of exposure

Mucous membrane (eye, mouth, nose)continuous irrigation with rapidly flowing water

or sterile saline for > 15 minutes

Skinscrub for at least 15 minutes while copiously

soaking the wound with soap or detergent solution fresh Dakin's solution (0.5% hypochlorite)

3 Levels of RiskCasual contacts:

Remote contact (same airplane/hotel)No surveillance indicated

Close contacts:Housemates, nursing personnel, shaking hands,

hugging, handling lab specimensPlace under surveillance when diagnosis

confirmedRecord temperatures twice daily x 3 wksNotify for temperature >=101

MMWR 1988;37:1-16

3 Levels of RiskHigh-risk:

Mucous membrane contact (kissing, sex) or needle stick or other penetrating injury involving blood/body fluid

Place under surveillance as soon as diagnosis is considered

Immediately isolate for temperature >= 101

MMWR 1988;37:1-16

Know What to Do for Yourself and Others

Medical Management

The foundation of treatment is supportive care

• Hemodynamic resuscitation & monitoring• Careful management of fluid and electrolytes,

blood pressure, and circulatory volume – Use of colloid– Hemodialysis or hemofiltration as needed

Esp. HFRS patients

• Vasopressors and cardiotonic drugs (some cases do not respond to i.v. fluids)

• Cautious sedation and analgesia

Medical Management

Disseminated Intravascular Coagulation (DIC) may be important in some VHFs (RVF, CCHF, filoviruses)

Coagulation studies and clinical judgment as guideReplacement of coagulation factors / cofactorsPlatelet transfusions

No aspirin, NSAIDs, anticoagulant therapies, or IM injections

Medical ManagementAntiviral Therapy

Ribavirin Investigational drug, compassionate use Contraindicated in pregnancy Arenaviridae (Lassa, AHF, BHF) Bunyaviridae (HFRS, CCHF) – not RVF NO UTILITY FOR FILOVIRUSES OR FLAVIVIRUSES

Immune (convalescent) plasma Arenaviridae (AHF & BHF; ?Lassa) Passive immunoprophylaxis post-exposure? Experimental studies in animals have not proven

efficacy against filovirus infection NOT READILY AVAILABLE

Medical Management For Arenavirus & Bunyavirus

Ribavirin Treatment30 mg/kg IV single loading dose 16 mg/kg IV q 6 hr for 4 days8 mg/kg IV q 8hr for 6 days

Prophylaxis500 mg PO q 6 hr for 7 days (different regimens)

Note: Parenteral (Rx) and oral Ribavirin (PEP) are investigational and available only through human use protocols (ahem….contact USAMRIID through ID consult) Borio L, et al. JAMA 287(18):2391-2405, 2002

McCormick JB et. al. N Eng J Med 314(1):20-26, 1986Jahrling PB et al. J Infect Dis 141:580-589, 1980

Filovirus Prophylaxis/TreatmentA number of therapies have been shown to

protect NHPs when begun shortly after filovirus exposure.Vaccination (recombinant VSV)Immunomodulators (rNAPc2 and rhAPC)Antivirals (siRNA and antisense molecules)Monoclonal antibodies

Pre-exposure prophylaxis with some vaccine platforms have demonstrated protection in NHPsVSV, Adenovirus vectored (with/without DNA prime)Virus-like ParticlesVEE replicon

None is approved for human use

No licensed treatments for filovirusesNeutralizing human monoclonal antibodies

Effective as pre and immediate (1 h) postexposure prophylaxis in guinea pigs (failed at 6 h postchallenge)

Equine IgG ineffective for monkeys (on day 0)Delay in viremia, but still diedSecond dose on day 5 no added benefit

JID 1999;179(Suppl1):S224-34 J Virol 2002;76:6408-12 Lancet 2003;362:1953-58.

Potential Options - EbolaNo consensus on utility of use of

immune convalescent plasmaMost case reportsNot readily available, safe source

Humans – limited data with blood transfusion from convalescent patients from Kikwit– 7/8 survive with Ebola c/w case fatality rate of 80%Survivors received better supportive care?Late in the epidemic, thus decreased

virulence?

JID 1999;179(Suppl1):S18-23JAMA 2002;287(18):2391-2405.

Medical Management of Hemorrhagic SyndromePotential of Activated Protein C (Xigris®)

VHF’s grouped by syndrome they produce – not by agent Activated protein C (rhAPC / Xigris®) targets the

syndrome.

rhAPC labeled for use in syndrome, not as a specific antiviral chemotherapeutic has no anti-EBOV activity in vitro.

Serves as: an exogenous source of activated protein C anti-thrombotic pro-fibrinolytic anti-inflammatory effects

Hensley et. al.: In publication 2007.

Medical Management of Hemorrhagic SyndromePotential of Activated Protein C (Xigris®)

DIC a common manifestation in several VHFs, especially filoviridae; rapid and significant depletion of endogenous

protein C

Significant declines in protein C levels also reported in patients with Argentine hemorrhagic fever.

Recent study at RIID: rhAPC (Xigris®) had beneficial effects in most

NHPs (including survival in 2) challenged w/ lethal dose of ZEBOV

Hensley et. al.: In publication 2007.

Medical Management of Hemorrhagic SyndromePotential of Xigris®

Approved Xigris dose in humans for severe sepsis is 24 g/kg/hr for 96 hrs. Highest NOAEL* (No Observed Adverse Event Level ) from toxicology studies in monkeys and in phase 1 studies is 48 g/kg/hr.

Disadvantages of Xigris: Administered by continuous I.V. infusion Short high-life Expensive (AND NO LONGER PRODUCED BY COMPANY) Potential for development of immune antibodies against

recombinant product

Not the “magic bullet”, but one possible component in combination therapy protocols for various VHFs.

Hensley LE, et. al.: In publication 2007.

Ebola virus induces overexpression of the pro-coagulant tissue factor in primate monocytes and macrophages

Inhibition of the tissue-factor pathway could ameliorate the effects of Ebola hemorrhagic fever

THE LANCET Vol 362 December 13, 2003

33% (3/9) survival rate in each treatment group (injection of rNAPc2 either 10 min or 24 hr post lethal Ebola exposure)

All but 1 control animal died

THE LANCET 362 December 13, 2003

Goal: forming PMO: mRNA duplexBlocks translation of viral mRNA and inhibiting viral

replication

Mice fully protected at 500 µg, with dose response at lower doses

Guinea pigs with best response at 96 hr postchallenge

Nonhuman primates – 3/4 survive after combination of oligomers used (VP24, VP35, L) one dies of bacterial infection

PLoS Pathogens 2006;2(1):0005-0013.

Be on alert for emerging infections…Lujo hemorrhagic fever (Zambia, South Africa)

4 out of 5 patients diedThe lone survivor received ribavirin

Alkhurma hemorrhagic fever (Saudi Arabi)Case fatality rate ~30%Considered to be tick bornHemorrhagic fever +/- encephalitis (similar to Kyasanur

Forest Disease)

Novel bunyaviruses (likely tick borne)Severe Fever with Thrombocytopenia Syndrome virus (China)Heartland virus (2 cases, no deaths; found in Missouri)

Avian influenzaH5N1 (case fatality rates ~30-60%)H7N9 (case fatality rate ~33% as of 11 AUG

2013)

Middle East Respiratory Syndrome Coronavirus (MERS-CoV)48% case fatality rate (as of 1 AUG 2013)

Be on alert for emerging infections… (not VHFs)

HenipavirusesNipah virus

Infects pigs Case fatality rate ~60-90% Movie “Contagion” based on this virus Flu-like respiratory illness with CNS involvement

Hendra virus Infects horses Case fatality rate ~60% Flu-like respiratory illness with CNS involvement

Be on alert for emerging infections… (not VHFs)

Final ThoughtsMaintain an index of suspicionBYOP (Bring your own PPE):

Masks, gowns, gloves, goggles, caps

Have an exit strategyDon’t let anyone use a non-sterile needle on

youRodent/bat controlGet WHO guidelines

HEPA Filter

In-line Air

Ear Plugs

Air Flow

Air Flow

Positive Pressure

Exhaust vents

Double Gloves

For which of the following viral infections would you not use ribavirin?

A. CCHFB. Junin (Argentine HF)C. LassaD. EbolaE. Hantaan (HFRS)

For which of the following viral infections would you not use ribavirin?

A. CCHFB. Junin (Argentine HF)C. LassaD. EbolaE. Hantaan (HFRS)

Questions1) Which of the following diseases should be

considered in the differential diagnosis of a viral hemorrhagic fever:

a) malariab) smallpoxc) typhoid feverd) leptospirosise) all of the above

Questions1) Which of the following diseases should be

considered in the differential diagnosis of a viral hemorrhagic fever:

a) malariab) smallpoxc) typhoid feverd) leptospirosise) all of the above

Questions2) What is the primary mechanism of human to

human transmission that has occurred in outbreaks of viral hemorrhagic fevers?

a) inhaled small droplet nuclei (respiratory aerosols)

b) percutaneous or mucus membrane contact with blood or body fluids of a victim

c) contact with urined) sharing the same householde) inhaled large droplets

Questions2) What is the primary mechanism of human to

human transmission that has occurred in outbreaks of viral hemorrhagic fevers?

a) inhaled small droplet nuclei (respiratory aerosols)

b) percutaneous or mucus membrane contact with blood or body fluids of a victim

c) contact with urined) sharing the same householde) inhaled large droplets

Questions3) What is the most important aspect for

preventing spread of viral hemorrhagic fevers in an outbreak?

a) isolating patients in a negative pressure roomb) caregivers use basic barrier methods (gloves,

masks, gowns, goggles)c) place the patient in a separate facility a

minimum of 20 foot distance from the primary care area

d) rapid treatment with an effective antiviral medication

e) vaccination of all close contacts

Questions3) What is the most important aspect for

preventing spread of viral hemorrhagic fevers in an outbreak?

a) isolating patients in a negative pressure roomb) caregivers use basic barrier methods

(gloves, masks, gowns, goggles)c) place the patient in a separate facility a

minimum of 20 foot distance from the primary care area

d) rapid treatment with an effective antiviral medication

e) vaccination of all close contacts

Match the virus with the sequelaa) Lassab) Rift Valley

Feverc) HFRSd) Yellow Fever

__Retinitis__Deafness__Icterus/Jaundice

__Renal failure

Match the virus with the sequelaa) Lassab) Rift Valley

Feverc) Hantaand) Yellow Fever

b_Retinitisa_Deafnessd_Icterus/Jaundice

c_Renal failure

Match the virus with the Countermeasurea)  Ebolab)  Lassa c)  Junind)  Yellow Fever

__Licensed vaccine

__Immune plasma__Ribavirin__Supportive Care

Match the virus with the countermeasurea)  Ebolab)  Lassa c)  Junind)  Yellow Fever

d_Licensed vaccine

c_Immune plasma

b_Ribavirina_Supportive care

Questions?

Thanks to:

COL Mark Kortepeter, MD, MPHDirector, Infectious Disease Clinical Research

Program